Poudel 2019 Can J Physiol Pharmacol
Poudel A, Zhou JY, Mekala N, Welchko R, Rosca MG, Li L (2019) Berberine hydrochloride protects against cytokine-induced inflammation through multiple pathways in undifferentiated C2C12 myoblast cells. Can J Physiol Pharmacol 97:699-707. |
Poudel A, Zhou JY, Mekala N, Welchko R, Rosca MG, Li L (2019) Can J Physiol Pharmacol
Abstract: Obesity is associated with skeletal muscle insulin resistance and the development of metabolic syndrome. Undifferentiated skeletal muscle cells are sensitive to oxidative stress. Berberine hydrochloride (BBR) improves insulin resistance and exhibits anti-inflammatory properties. However, the underlying mechanism and the cell signaling pathways involved remain largely elusive. We therefore investigated the anti-inflammatory effects of BBR and the signaling pathways using skeletal C2C12 myoblast cells. Undifferentiated C2C12 myoblast cells were treated with interleukin-1Ξ² alone or in combination with tumor necrosis factor-Ξ± in the presence or absence of BBR. We found that BBR reduced the cytokine-induced expression of inducible nitric oxide synthase and stress-related kinases including p-38 mitogen-activated protein kinase, nuclear factor kappa B (NF-ΞΊB), and stress-activated protein kinases/Jun amino-terminal kinases (SAPK/JNK) in C2C12 myoblast cells. Furthermore, BBR reversed cytokine-mediated suppression of AMP-activated protein kinase (AMPKΞ±), sirtuin-1 (SIRT-1), and PPAR-Ξ³ coactivator-1Ξ± (PGC-1Ξ±). In addition, cytokine-induced reduction of mitochondrial marker proteins and function were rescued after BBR treatment. Catalase, an antioxidant enzyme, was elevated after BBR treatment. Our results demonstrate that BBR ameliorates cytokine-induced inflammation. The anti-inflammatory effect of BBR in skeletal progenitor cells is mediated through pathways including activation of the AMPKΞ±-SIRT-1-PGC-1Ξ±, inhibition of the mitogen-activated protein kinase 4 (MKK4)-SAPK/JNK-C-JUN, as well as protection of mitochondrial bioenergetics. BBR may be a potential medication for metabolic syndrome. β’ Keywords: Berberine, Cytokine, Inflammation, Insulin resistance β’ Bioblast editor: Plangger M β’ O2k-Network Lab: US OH Cleveland Rosca MG
Labels: MiParea: Respiration, Pharmacology;toxicology
Pathology: Obesity
Organism: Mouse Tissue;cell: Skeletal muscle Preparation: Permeabilized cells
Coupling state: LEAK, OXPHOS, ET
Pathway: N, S, NS, ROX
HRR: Oxygraph-2k
Labels, 2020-02